B6-hIL1RL1 Mice

Catalog Number: C001632

Strain Name: C57BL/6NCya-Il1rl1em1(hIL1RL1)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

The IL1RL1 gene, also known as ST2 or IL33R, encodes a member of the interleukin-1 receptor superfamily, specifically binding the cytokine IL-33, a key mediator of inflammation and immunity [1]. This gene produces two primary protein isoforms: transmembrane ST2L and soluble sST2. ST2L, the functional receptor, is expressed on immune cells, including mast cells, helper T cells, and eosinophils, as well as epithelial and endothelial cells [1]. Upon IL-33 binding, ST2L activation initiates NF-κB and MAPK inflammatory signaling cascades, leading to the release of cytokines and chemokines that drive type II inflammation, fibrosis, and tumor microenvironment modulation [1-4]. The IL-33/ST2 axis exhibits context-dependent functions in tumors, potentially promoting proliferation, metastasis, and angiogenesis, or conversely, activating anti-tumor immunity and suppressing tumor growth [2]. Polymorphisms in IL1RL1 have been associated with increased susceptibility to a range of diseases, including asthma, allergies, cardiovascular diseases, inflammatory bowel disease, and cancers [1-5]. Consequently, the IL-33/ST2 signaling pathway has emerged as a focus of intense research for therapeutic intervention in diverse pathologies, with IL1RL1 representing a potential target for the development of novel therapies for cancer, inflammatory, and immune-related diseases [1-5].

The B6-hIL1RL1 mouse is a humanized model constructed using gene editing technology, where the mouse IL1RL1 signal peptide and endogenous extracellular domain (aa.1~332) were replaced with the human IL1RL1 signal peptide and extracellular domain (aa.1~328). The murine IL1RL1 transmembrane and cytoplasmic region (aa.333~567) were preserved. Homozygous B6-hIL1RL1 mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of cancer, inflammatory, and immune-related diseases, and for the development of IL1RL1-targeted drugs.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hIL1RL1 mice. The mouse Il1rl1 signal peptide and endogenous extracellular domain (aa.1~332) were replaced with the human IL1RL1 signal peptide and extracellular domain (aa.1~328). The murine transmembrane and cytoplasmic region (aa.333~567) were preserved.

 

Application

  • IL1RL1-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of cancer, inflammatory, and immune-related diseases.

 

References
[1]Griesenauer B, Paczesny S. The ST2/IL-33 Axis in Immune Cells during Inflammatory Diseases. Front Immunol. 2017 Apr 24;8:475.
[2]Andreone S, Gambardella AR, Mancini J, Loffredo S, Marcella S, La Sorsa V, Varricchi G, Schiavoni G, Mattei F. Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight. Front Immunol. 2020 Nov 30;11:571593.
[3]Yi XM, Li M, Chen YD, Shu HB, Li S. Reciprocal regulation of IL-33 receptor-mediated inflammatory response and pulmonary fibrosis by TRAF6 and USP38. Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2116279119.
[4]Saikumar Jayalatha AK, Hesse L, Ketelaar ME, Koppelman GH, Nawijn MC. The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention. Pharmacol Ther. 2021 Sep;225:107847.
[5]Trindade SC, Lopes MPP, Oliveira TTMC, Silva MJ, Queiroz GA, Jesus TS, Santos EKN, Carvalho-Filho PC, Falcão MML, Miranda PM, Santos RPB, Figueiredo CA, Cruz ÁA, Seymour GJ, Gomes-Filho IS. Single nucleotide variants in the IL33 and IL1RL1 (ST2) genes are associated with periodontitis and with Aggregatibacter actinomycetemcomitans in the dental plaque biofilm: A putative role in understanding the host immune response in periodontitis. PLoS One. 2023 Mar 22;18(3):e0283179.